Abstract:
:The purpose of this study was to investigate the influence of molecular shape, conformability, net surface charge and tissue interaction on transscleral diffusion. Unfixed, porcine sclera was clamped in an Ussing chamber. Fluorophore-labelled neutral albumin, neutral dextran, or neutral ficoll were placed in one hemi-chamber and the rate of transscleral diffusion was measured over 24 h using a spectrophotometer. Experiments were repeated using dextrans and ficoll with positive or negative net surface charges. Fluorescence recovery after photobleaching (FRAP) was undertaken to compare transscleral diffusion with diffusion through a solution. All molecules were 70 kDa. With FRAP, the diffusion coefficient (D) of neutral molecules was highest for albumin, followed by ficoll, then dextran (p < 0.0001). Positive dextrans diffused fastest, followed by negative, then neutral dextrans (p = 0.0004). Neutral ficoll diffused the fastest, followed by positive then negative ficoll (p = 0.5865). For the neutral molecules, transscleral D was highest for albumin, followed by dextran, then ficoll (p < 0.0001). D was highest for negative ficoll, followed by neutral, then positive ficoll (p < 0.0001). By contrast, D was highest for positive dextran, followed by neutral, then negative dextran (p = 0.0021). In conclusion, diffusion in free solution does not predict transscleral diffusion and the molecular-tissue interaction is important. Molecular size, shape, and charge may all markedly influence transscleral diffusion, as may conformability to a lesser degree, but their effects may be diametrically opposed in different molecules, and their influence on diffusion is more complex than previously thought. Each variable cannot be considered in isolation, and the interplay of all these variables needs to be tested, when selecting or designing drugs for transscleral delivery.
journal_name
Exp Eye Resjournal_title
Experimental eye researchauthors
Srikantha N,Mourad F,Suhling K,Elsaid N,Levitt J,Chung PH,Somavarapu S,Jackson TLdoi
10.1016/j.exer.2012.07.007subject
Has Abstractpub_date
2012-09-01 00:00:00pages
85-92eissn
0014-4835issn
1096-0007pii
S0014-4835(12)00193-5journal_volume
102pub_type
杂志文章abstract::We showed previously that treatment of cultured rabbit lens epithelial cells (LECs) with hyperbaric oxygen (HBO) produced DNA strand-breaks, caused reversible inhibition of protein synthesis and induced the synthesis of a 32 kD protein. In the present work, we employed immunostaining procedures to identify the 32 kD p...
journal_title:Experimental eye research
pub_type: 杂志文章
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abstract::Several lines of evidence support the existence of a renin-angiotensin system (RAS) in the retina that is separated from the blood stream by the retinal pigment epithelium (RPE). Under physiological conditions, increased activity of intraretinal RAS regulates neuronal activity of the retina but patho-physiologically p...
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journal_title:Experimental eye research
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doi:10.1016/j.exer.2008.01.008
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abstract::It has long been assumed that unstimulated tears are more thoroughly equilibrated with epithelial secretions than stimulated tears, since they are in contact with tarsal, bulbar and corneal surfaces for longer. It was also believed from results with model solutions that soluble mucin is responsible for the observed su...
journal_title:Experimental eye research
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abstract::The supply of L-carnosine, a bioactive dipeptide of β-alanine and l-histidine, to the retina across the blood-retinal barrier (BRB) was studied. The in vivo and in vitro studies revealed low uptake activities for [(3)H]Gly-Sar, a representative dipeptide, suggesting that l-carnosine transport plays only a minor role a...
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(92)90151-h
更新日期:1992-06-01 00:00:00
abstract::This study was undertaken to develop a feline model of corticosteroid-induced ocular hypertension. In the first experiment, eight cats were selected whose intraocular pressure (17 +/- 0.4 mmHg) was consistently below the mean baseline intraocular pressure of our colony (24 +/- 0.5) during the preceding 2 months. Unila...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/s0014-4835(05)80210-6
更新日期:1992-02-01 00:00:00
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journal_title:Experimental eye research
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更新日期:1987-03-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.2000.0901
更新日期:2000-11-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(91)90079-t
更新日期:1991-08-01 00:00:00
abstract::The elimination of spermine, the end product of cellular polyamine, from the retina to the blood across the blood-retinal barrier (BRB) was investigated. The in vivo microdialysis study revealed that the elimination of [(3)H]spermine from vitreous humor after vitreous bolus injection was in a biexponential manner. The...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2014.05.002
更新日期:2014-07-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
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更新日期:1989-06-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.1999.0700
更新日期:1999-10-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/0014-4835(85)90109-5
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2017.02.012
更新日期:2017-06-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2020.108305
更新日期:2021-01-01 00:00:00
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2018.04.006
更新日期:2018-07-01 00:00:00
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journal_title:Experimental eye research
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journal_title:Experimental eye research
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2013.03.002
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.1996.0194
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abstract::The similarities between glaucoma and mitochondrial optic neuropathies have driven a growing interest in exploring mitochondrial function in glaucoma. The specific loss of retinal ganglion cells is a common feature of mitochondrial diseases - not only the classic mitochondrial optic neuropathies of Leber's Hereditary ...
journal_title:Experimental eye research
pub_type: 杂志文章,评审
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journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2009.06.013
更新日期:2009-11-01 00:00:00
abstract::Albino mice exposed to 1 X 10(-4) W cm-2 of UV radiation in the range 290-400 nm for 12 hr per day developed anterior lens opacities within 1-2 months after onset of the exposure. Histological changes demonstrated marked derangement of the lens epithelium. When the radiation was filtered with glass, eliminating radiat...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/s0014-4835(85)80011-7
更新日期:1985-10-01 00:00:00
abstract::The pink-eyed dilution (p) locus is known to control the quantity of melanin pigment made within melanocytes and retinal pigment epithelium (RPE) in the eye. We have examined the effects of several mutant allele combinations at the murine p locus on the number and morphology of melanosomes in choroidal melanocytes and...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1006/exer.1998.0599
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abstract::Recent evidence suggests that mucosal epithelial cells are capable of actively participating in immune reactions via expression of surface antigens, such as adhesion molecules, and synthesis of cytokines. This appears to be important in the pathophysiology of non-ocular allergic disorders. The objectives of the experi...
journal_title:Experimental eye research
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doi:10.1006/exer.1998.0528
更新日期:1998-11-01 00:00:00
abstract::Several variants of growth hormone (GH) are found in the retina and vitreous of the chick embryo, where they appear to act as cell survival factors, having neuroprotective effects on retinal ganglion cells (RGCs). Here, we investigate the molecular mechanisms of the anti-apoptotic effect of GH in cultured RGCs. GH tre...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2006.06.009
更新日期:2006-11-01 00:00:00
abstract::Research with animal models of Pseudomonas aeruginosa keratitis has shown that use of a topical corticosteroid alone against an established infection can significantly increase the number of colonizing bacteria or worsen clinical disease. Moreover, retrospective analysis has suggested that corticosteroid use in humans...
journal_title:Experimental eye research
pub_type: 杂志文章
doi:10.1016/j.exer.2018.10.010
更新日期:2019-02-01 00:00:00